One of the greatest difficulties encountered in the surgical therapies of cancers is the post-operative recurrence. In many cases, metastasis is the primary cause of such recurrence. Metastasis involves a series of complex reactions, inclusive of separation of cancer cells from the primary nidus, followed by infiltration into the surrounding tissues, and proliferation at distant sites of the body to thereby form the secondary, metastasized nidi.
Cancer cells, even after separation from the primary nidus, are hindered from further spreading by the nearby existing extracellular matrix composed of sugar proteins, such as various collagens, fibronectins and laminins, proteoglycans, etc. Cancer cells, on the other hand, cleave and degrade the extracellular matrix structure and migrate, while taking full advantage of a variety of proteases and glycosidases secreted by themselves or the interstitium cells.
Cancer cells having separated in this manner from the primary nidus invade the vasculature, then travel to distant organs, infiltrate into the basement membrane of vascular endothelia and finally lodge in distant tissues for proliferation.
Consequently, suppression of metastasis bears great importance as a one of cancer therapies. For the purpose of this, there have so far been developed various metastasis suppressory agents, such as platelet aggregation suppressory agents, matrix metalloproteinase inhibitors and adhesion-factor suppressory agents. Nevertheless, these have not turned out to provide any effective means for suppressing metastasis.